Effect of Demographic Factors on Quality of Life in Children with ADHD under Atomoxetine Treatment: 1-Year Follow-up

Abstract Attention-deficit hyperactivity disorder (ADHD) is the most common psychiatric disorder in children and adolescents. Symptoms of ADHD and its treatment can impact an individual's quality of life (QoL). The present study aimed to evaluate the effect of atomoxetine treatment, demographic characteristics, and seasonal variation on QoL in children with a recent diagnosis of ADHD and their parents. The present study included a cohort of 200 children diagnosed with ADHD. In addition to the recruited children, one of their parents was included in the study. ADHD symptoms were assessed using Conners' Parent Rating Scale. QoL of the participants was assessed with the PedsQL, while parents' QoL was evaluated using the World Health Organization Quality of Life questionnaire (WHOQOL-Bref). There was significant improvement in pediatric and parental QoL after treatment with atomoxetine. Significant factors related to better QoL in the participants included spring season, above average Conner's score, male sex, and rural residence. However, after using multivariate regression analysis, only patients' sex and Conner's score were significant predictors of pediatric QoL at the end of treatment with atomoxetine. Medical treatment significantly improved QoL in children with ADHD and their parents. Level of improvement was affected by patients' sex and ADHD severity.


Introduction
Attention-deficit hyperactivity disorder (ADHD) is the most common psychiatric disorder in children and adolescents. It is characterized by behavioral problems such as attention deficit, hyperactivity and impulsivity. 1 Assessment should include careful history taking thorough physical examination and psychological evaluation. Stimulant medications are effective for treatment. However, their side effects and potential of misuse and abuse constitute significant concerns. 2 Some demographic characteristics are linked to increased prevalence of ADHD. It is known that ADHD is more common and is characterized by more severe symptoms in males. 3 It was also suggested that poor socioeconomic status (SES) increases children's risk of ADHD. 4 In addition, it was found that genetic and environmental factors play a role in the causation and development of ADHD. 5 A pattern of increasing prevalence of ADHD has been suggested to be partly linked to exposure to environmental pollutants. 6 Moreover, it was noted that seasonal and Keywords ► attention deficit hyperactivity disorder ► quality of life ► seasonal variation Abstract Attention-deficit hyperactivity disorder (ADHD) is the most common psychiatric disorder in children and adolescents. Symptoms of ADHD and its treatment can impact an individual's quality of life (QoL). The present study aimed to evaluate the effect of atomoxetine treatment, demographic characteristics, and seasonal variation on QoL in children with a recent diagnosis of ADHD and their parents. The present study included a cohort of 200 children diagnosed with ADHD. In addition to the recruited children, one of their parents was included in the study. ADHD symptoms were assessed using Conners' Parent Rating Scale. QoL of the participants was assessed with the PedsQL, while parents' QoL was evaluated using the World Health Organization Quality of Life questionnaire (WHOQOL-Bref). There was significant improvement in pediatric and parental QoL after treatment with atomoxetine. Significant factors related to better QoL in the participants included spring season, above average Conner's score, male sex, and rural residence. However, after using multivariate regression analysis, only patients' sex and Conner's score were significant predictors of pediatric QoL at the end of treatment with atomoxetine. Medical treatment significantly improved QoL in children with ADHD and their parents. Level of improvement was affected by patients' sex and ADHD severity. circadian rhythm instabilities can significantly influence ADHD symptoms. 7 Symptoms of ADHD can negatively impact an individual's health and quality of life (QoL) and impair function in multiple settings. 8 Furthermore, this disorder creates significant difficulties in education, social performance, and personal relationships. 9 Factors related to QoL in children with ADHD include gender, 10 SES, 11 and type of treatment. 12 The present study aimed to evaluate the effect of demographic characteristics and seasonal variation on QoL in children with ADHD and their parents.

Patients and Methods
The present prospective study included a cohort of 200 newly diagnosed, treatment-naive children with combined-type ADHD recruited from the outpatient clinic of Ain Shams University Hospitals. The study protocol was approved by the local ethical committee and the legal guardians of all included children gave informed consent to participate in the study. In addition to the recruited children, one of the child's parents were included in the study.
The children included in the study were 6 to 12 years old and their diagnosis of ADHD was based on Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria. Exclusion criteria were associated chronic clinical conditions, such as "diabetes and thyroid abnormalities," or other neurodevelopmental disorders, such as "autism spectrum and seizure disorders," and intake of other medications.
All patients were subjected to careful history taking and thorough clinical examination. SES was assessed using an Egyptian validated scale. The scale comprises various socioeconomic parameters including income, education, housing, etc. 13 Patients received medical treatment in the form of oral atomoxetine capsules (0.5 mg/kg/day as initial dose increased after a minimum of 3 days to 1.2 mg/kg/day with a maximum daily dose of 1.4 mg/kg/day or 100 mg/day). In addition, patients were subjected to cognitive behavioral therapy sessions.
ADHD symptoms were assessed using Conners' Parent Rating Scale short form Arabic version (CPRS-48), 14 which is a 48-item questionnaire. Each item is evaluated using 4point Likert's scale (from 0 denoting not at all to 3 denoting severely affected). CPRS-48 has seven subscales which are conduct problem (eight items), learning problem (four items), psychosomatic problem (four items), impulsive-hyperactivity (four items), and anxiety (four items), hyperactivity index (10 items), and inattention (eight items). QoL of the studied children was assessed by the Arabic version of PedsQL 4.0 Generic Core Scales (physical, emotional, social, school functioning) 15 while parents' QoL was evaluated using the Arabic version of WHO QoL-BREF instrument. 16 Patients were followed-up for a complete calendar year from September 22, 2018 through September 21, 2019. None of the patients studied were lost to follow-up. Patients' QoL was assessed at baseline (i.e., before treatment) and at the end of every season.
Data obtained from the present study were presented as mean AE standard deviation (SD), median and interquartile range (IQR) or number and percent. Statistical comparisons were achieved using t-test, Mann-Whitney U-test, one-way analysis of variance (ANOVA), Kruskall-Wallace test, Fisher's exact test or Chi-square test as appropriate. Regression analysis was used to identify predictors of pediatric QoL. A p-value less than 0.05 was considered statistically significant.
After 1 year of treatment, the total pediatric QoL score significantly improved in comparison to the pretreatment levels: ►Table 4 illustrates the association between pediatric QoL and demographic and clinical data. There was significant association between improved total pediatric QoL scores after treatment and spring season, above average Conners' score of ADHD, male sex of patients, and rural residence. On multivariate regression analysis, significant predictors of QoL included patients sex (odds ratio [OR] ¼ À 5.1, 95% confidence interval [CI]: À6.2 to À4.0, p < 0.001) and Conners' score (OR ¼ À 2.1, 95% CI: À3.0 to À1.1, p < 0.001; ►Table 5).

Discussion
The current study revealed significant improvement of pediatric QoL and its individual domains after treatment with atomoxetine. These results are consistent with multiple previous studies. In the study of Haynes et al 17 on approximately 700 children with ADHD, atomoxetine treatment was associated with improved QoL over 2 years. In another study, it was found that atomoxetine withdrawal resulted in significant deterioration of QoL parallel to the changes in ADHD symptoms. 18 In addition, it was found that parents of the studied children experienced significant improvement of their QoL; a finding that accords with the conclusions of Escobar et al 19 who noted that the positive impact of atomoxetine on children QoL was associated with a corresponding positive influence on their parents.
In the present study, it was found that the spring season has the most significant impact on patients' QoL. The improved QoL in spring may be related to improved sun exposure and increased vitamin D levels. This explanation may be supported by findings of other reports. In one recent study, vitamin-D deficiency was associated with ADHD symptoms in children. 20 One recent meta-analysis confirmed these conclusions. 21 Of note, the study of Wynchank et al 7 found that worsening of ADHD symptoms in autumn and/or winter may be attributed the association between ADHD and seasonal affective disorder (SAD) commonly seen in adult patients with ADHD. However, the prevalence of SAD is much lower in children as compared with adults. 22 Moreover, children with SAD were excluded from the present study.
In this study, it was found that the children with below average Conners' score had significantly lower QoL. The association between ADHD symptoms severity and QoL was reported by the study of Mulraney et al 23 on 392 children with ADHD assessed at three time points (0, 6, and 12 months). The study found that parent-reported ADHD symptoms predicted poor QoL at each subsequent time point.
Assessment of the relation between children QoL and various demographic data revealed significantly all-year and seasonal lower QoL in female children after treatment. In harmony with these results, the study of Dallos et al 24 on Table 2 Basic data of the studied parents (n ¼ 200) 178 children with ADHD found that lower self-reported QoL was associated with female gender. This may be related to the less severe form of ADHD symptoms in males probably due to the protective effects of testosterone. 25 In addition, the present study found significantly higher QoL after treatment in children living in rural areas. This finding may be surprising in respect to the lower rate of utilization of ADHD medications in rural areas. 26,27 However, the better QoL in children with ADHD living in rural areas may be related to lower pollution rates. 28,29

Limitations
Results of the present study are limited by the lack of comparison between children with ADHD under atomoxetine and those under other types of pharmacological and nonpharmacological treatment.

Conclusion
In conclusion, we revealed significant improvement of QoL in children with ADHD and their parents. Improvement is more pronounced in the spring, in male patients, and in patients with less severe ADHD symptoms.

Funding
None.